Lec 55: Pharmacokinetics I Flashcards

1
Q

Zero order kinetics

A

constant rate of absorption or elimination

-LINEAR, M=kt

  • speed is constant, rate of absorptionis independent of concentration gradient
  • transport mechanism is saturated
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2
Q

First order kinetics

A
  • rate is proportional to the amount of drug still unabsorbed
  • EXPONENTIAL, M= Mo(e)^(-kt)
  • increase difference:increase speed
  • [ ] is major determinant, gradient counts!
  • not constant amount, constant fraction
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3
Q

order Applications: Drug Absorption/Drug Elimination

A

zero order elimination - duration of a therapeutically effective drug [] increases linearly with amount in body fluids
first order elimination - duration of a therapeutically effective drug [] increases as the log of the amount in the body fluids does

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4
Q

half life equation

A

half life = 0.693/ke

ke=rate constant of elimination

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5
Q

Volume of Distribution

A

-apparent Volume in which the drug is distributed (a concept, not a real number)

Vd=(mg drug in body)/([]in plasma mg/L)

  • as plasma [] decreases, Vd increases
  • can be much higher than the total body volume if drug is nonhomogenously distributed with high [] in extravasculartissues (plasma [ ] is low in this case)
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6
Q

Clearance

A
  • expressed in L/hr or mL/min
  • Volume of plasma cleared of drug
  • CL is additive

CL=(rate of elimination in mg/hr)/([] drug in mg/L)

CL=(ke)(Vd)
half life=0.693
Vd/CL

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7
Q

Bioavailability

A

-fraction of unchanged drug reaching systemic circulation after oral administation (F)

F=f(1-ER)

ER= extraction ration in liver
f=fraction absorbed from gut

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8
Q

Extent of absorption

A

ratio of drug entering blood circulation to total drug in digestive system
rate= extent *time

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9
Q

First Pass Elimination

A

presystemic hepatic elimination; passes through liver before system circulation and may be metabolized or excreted into bile

-drug is decreased by : QCi - QCo, where Q= 90 L/h hepatic blood flow and Ci=drug entering liver, and Co = drug leaving

Hepatic CL= Q*ER

***if ER is large, we can compensate for low oral bioavailability by 1) increasing dose and 2) use alternative administative routes

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10
Q

accumulation factor of a drug when the dosing interval is shorter than four half-live

A

accumulation factor = 1/(fraction lost in one dosing interval)

example: for a drug given once every half life, AF=2

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11
Q

Dosing Regimen Construction

A
  1. identify target [] that will produce desired effect - [] range between that causing ½ of greatest therapeutic effect (lower limit) and [] that will cause side effects in no more than 5-10% of all patients (uppe rlimit)
  2. determine Vd and CL
  3. maintenance dose
    a. dosing rate = CL*Css , where Css= []at steady state
  4. if intermittent doses are given, then maintenance dose is determined by:maintenance dose=dosing rate* dosing interval
  5. if target [] needs to be reached quick, and or elimination rate ke is small, loading doses might be applied: loading dose= Vd*Target []
  6. check for desired effect and adjust
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12
Q

Relate half lives to steady state

A

It takes 4-5 half lives to reach/change a steady state

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